Hepatic expression of tumor necrosis factor-α and evaluation of MAPK-p38 and NFκB signaling pathways in autoimmune hepatitis.

OBJECTIVES: Autoimmune hepatitis (AIH) is a necroinflammatory disease that occurs when genetically susceptible individuals are exposed to an environmental trigger. It is a rare disease, and its epidemiological aspects are nearly unknown in Northeast Brazil. In the literature, the activation of components of the inflammatory cascade pathways, including interleukins such as TNF-α and signaling factors like MAPK-p38 and NFκB, in the pathogenesis of AIH is well described in animal models. This study evaluated, for the first time, the immunostaining of TNF-α, MAPK-p38, and NFκB in immunohistochemical analysis of liver biopsies from AIH patients. The activation of the MAPK-p38 pathway was also studied through immunoassay analysis in the peripheral blood of AIH patients. METHODS AND RESULTS: Data from medical records of 25 AIH patients were analyzed. Histological and immunohistochemical analysis of liver tissue obtained from biopsies was performed to detect NFκB, MAPK-p38, and TNF-α. Immunoassay analysis of the MAPK-p38 pathway was performed in peripheral blood from 18 AIH patients and 8 healthy volunteers. Medical record analysis showed an average age of 33.3 years, with a female predominance in a ratio of 7.3:1. Concomitance with other autoimmune diseases was observed in 36 % of patients, with thyroid disorders being the most prominent among them, and an 8 % indication for liver transplantation. In the evaluation of autoantibodies, ANA was detected in 52 %, followed by SMA at 20 %, and Anti-LKM-1 at 16 %. Liver biopsy findings were like the global literature, with interface hepatitis and lymphoplasmacytic infiltration observed. Immunohistochemical analysis showed immunostaining for NFκB, MAPK-p38, and TNF-α, corroborating the inflammatory and immunological characteristics of the disease. Immunoassay analysis in peripheral blood confirmed the activation of the MAPK-p38 signaling pathway, with a statistically significant difference between AIH patients and healthy controls. CONCLUSIONS: The epidemiological and histological findings of AIH in this study in Northeast Brazil were like global population data. Immunohistochemical analysis of liver tissue and immunoassay analysis in peripheral blood confirmed the activation of TNF-α and the NFκB and MAPK-p38 signaling pathways in AIH patients.

Patients with fibromyalgia present different pain phenotypes compared to patients with generalized pain / Pacientes com fibromialgia apresentam fenótipos de dor diferentes em comparação com pacientes com dor generalizada

ABSTRACT BACKGROUND AND OBJECTIVES Fibromyalgia and generalized pain represent a global health problem and are distinct musculoskeletal disorders, but there is an overlap in the clinical presentation between these conditions. However, no study has compared pain characteristics between patients with fibromyalgia and patients with generalized pain. Therefore, the present study aimed to compare pain characteristics and functional limitation of patients with fibromyalgia and patients with generalized pain. METHODS A pre-planned secondary analysis of data collected from 311 patients with musculoskeletal pain was performed. Pain characteristics included pain intensity, pain duration, pain area, symptoms of central sensitization, presence of neuropathic-like symptoms, and the conditioned pain modulation. The Patient-Specific Functional Scale assessed functional limitation. RESULTS 98 patients with generalized pain were identified, being 58 (59.18%) classified in the fibromyalgia group and 40 (40.82%) classified in the generalized pain group. Significant differences were found between groups for Widespread Pain Index, Symptom Severity Scale, and Polysymptomatic Distress Scale. Participants with fibromyalgia presented higher values of pain intensity (fibromyalgia = 7.29±2.07, generalized pain = 6.05±2.47; p=0.008), neuropathic-like symptoms (fibromyalgia = 17.74±7.62, generalized pain = 12.17±6.41; p=0.005), and symptoms of central sensitization (fibromyalgia = 51.32±14.26, generalized pain = 33.97±14.65; p<0.001), when compared with generalized pain. There was no significant difference in conditioned pain modulation and functional limitation between groups. CONCLUSION Patients with fibromyalgia exhibited unfavorable pain characteristics, including pain intensity, neuropathic-like symptoms, and symptoms of central sensitization compared to patients with generalized pain. However, pain duration, functional limitation, and conditioned pain modulation did not present meaningful differences between groups.

RESUMO JUSTIFICATIVA E OBJETIVOS Fibromialgia e dor generalizada representam um problema de saúde global e são distúrbios musculoesqueléticos distintos, mas há uma sobreposição na apresentação clínica entre essas condições. Entretanto, nenhum estudo comparou as características da dor entre os pacientes com estas condições. Portanto, o presente estudo teve como objetivo comparar as características da dor e a limitação funcional de pacientes com fibromialgia e dor generalizada. MÉTODOS Realizou-se uma análise secundária pré-planejada de dados coletados de 311 pacientes com dor musculoesquelética. As características da dor incluíram: intensidade da dor, duração da dor, área da dor, sintomas de sensibilização central, presença de sintomas neuropáticos e a modulação condicionada da dor. A escala de funcionalidade específica do paciente avaliou a limitação funcional. RESULTADOS Identificou-se 98 pacientes com dor generalizada, sendo 58 (59,18%) classificados no grupo de fibromialgia e 40 (40,82%) no grupo de dor generalizada. Diferenças significativas foram encontradas entre os grupos para o índice de dor generalizada, escala de severidade de sintomas e escala polissintomática de sofrimento. Os participantes com fibromialgia apresentaram maiores valores de intensidade da dor (fibromialgia = 7,29±2,07, dor generalizada = 6,05 ± 2,47; p=0,008), sintomas neuropáticos (fibromialgia = 17,74±7,62, dor generalizada = 12,17 ± 6,41; p=0,005) e sintomas de sensibilização central (fibromialgia = 51,32±14,26, dor generalizada = 33,97±14,65; p<0,001), quando comparados à dor generalizada. Não houve diferença significativa na modulação condicionada da dor e na limitação funcional entre os grupos. CONCLUSÃO Pacientes com fibromialgia exibiram características de dor desfavoráveis, incluindo intensidade de dor, sintomas neuropáticos e sintomas de sensibilização central, quando comparados a pacientes com dor generalizada. Entretanto, a duração da dor, a limitação funcional e a modulação condicionada da dor não apresentaram diferença significativa entre os grupos.

Use of the painDETECT to discriminate musculoskeletal pain phenotypes.

BACKGROUND: Musculoskeletal pain patients present similar pain characteristics regardless of the clinical diagnosis. PainDETECT questionnaire is useful for screening neuropathic-like symptoms in many musculoskeletal conditions. However, no previous studies compared pain phenotypes of patients with musculoskeletal pain using the painDETECT. Therefore, the current study aimed to compare the pain characteristics of patients with musculoskeletal pain classified according to the painDETECT as nociceptive pain, unclear, and neuropathic-like symptoms. METHODS: A cross-sectional study was conducted in 308 participants with musculoskeletal pain. Demographic and clinical characteristics of the participants were examined. Neuropathic-like symptoms, pain intensity, pain area, Central Sensitization-related sign and symptoms, functional limitation, and conditioned pain modulation were assessed in patients with musculoskeletal pain. Independent one-way analysis of variance (ANOVA) was used to test for between-group differences for the outcome measures with continuous variables and Pearson chi-square test verified between-group differences on the efficiency of the conditioned pain modulation. RESULTS: Participants had a mean age of 52.21 (±15.01) years old and 220 (71.42%) were females. One hundred seventy-three (56.16%) participants present nociceptive pain, 69 (22.40%) unclear, and 66 (21.42%) neuropathic-like symptoms. A one-way ANOVA showed differences for the pain intensity [F (2,305) = 20.097; p < .001], pain area [F (2,305) = 28.525; p < .001], Central Sensitization-related sign and symptoms [F (2,305) = 54.186; p < .001], and functional limitation [F (2,256) = 8.061; p < .001]. However, conditioned pain modulation was similarly impaired among the three groups (X2 = 0.333, p = 0.847). CONCLUSION: Patients with neuropathic-like symptoms revealed unfavorable pain characteristics compared to their counterparts, including pain intensity, generalized pain, Central Sensitization-related sign and symptoms, and functional limitation.

Central Sensitization Inventory is a useless instrument for detection of the impairment of the conditioned pain modulation in patients with chronic musculoskeletal pain.

OBJECTIVE: The current study aimed to evaluate the concurrent validity and the diagnostic accuracy of the Central Sensitization Inventory (CSI) in detecting the impairment of the pain modulation in patients with chronic musculoskeletal pain. METHODS: A cross-sectional study was conducted in 267 patients with chronic musculoskeletal pain enrolled consecutively in an outpatient department. The CSI (index method) were compared with the cold pressor test, which was the psychophysical test used to assess the conditioned pain modulation (CPM), (reference standard). Spearman's correlations assessed the concurrent validity, and measurements of the diagnostic accuracy were performed. RESULTS: Ninety-three (34.8%) patients had CSI scores≥40. No significant correlation was found between CSI findings and the results of the CPT (dorsal forearm site or tibialis anterior site) was found. The cutoff point of 40 of the CSI showed values of sensitivity (35.1%, 95% CI: 22.6, 49.3) and specificity (65.2%, 95% CI: 58.4, 71.6) below 70%, and an accuracy of 59.1 (95% CI: 53.0, 65.1) when compared to the CPT to detect deficit. The ROC curve analysis yielded an area under the curve of 0.54 (95% CI: 0.45, 0.63, P>0.05). CONCLUSIONS: The CSI is a useless instrument to detect the deficit in the CPM in patients with chronic musculoskeletal pain due to the absence of correlation with the psychophysical test result and the insufficient measurements of diagnostic accuracy.

Aspectos humanistas, existenciais e fenomenológicos presentes na abordagem centrada na pessoa / Humanistic, existencial and phenomenological aspects in person centered approach

A Abordagem Centrada na Pessoa (ACP) é considerada uma das correntes identificadas com a Terceira Força em Psicologia ou Psicologia Humanista. Há aspectos significativos que correlacionam o pensamento do seu fundador, Carl Rogers, com alguns pressupostos da psicologia humanista e da filosofia existencialista. Mesmo que seu trabalho não tenha sido orientado pela fenomenologia, percebe-se em sua obra, desdobrada em várias fases, a prática de uma atitude desta natureza. Considerar, portanto, a ACP como uma abordagem humanista, existencial e fenomenológica remete-nos a uma série de questões relacionadas: 1) o que se entende por humanista? 2) Por consequência, o que é ser humano nesta perspectiva? 3) Como pensar o humanismo na psicologia? 4) Quais aspectos derivados da fenomenologia e do existencialismo encontram ressonância com a teoria e o método da ACP? Este artigo tem como objetivo contribuir na reflexão sobre as possíveis correlações entre essas perspectivas filosóficas e a Abordagem Centrada na Pessoa, tema ainda controverso no contexto brasileiro mesmo diante da diversidade teórica e de perspectivas que esta abordagem vem assumindo na atualidade.(AU)

Person Centered Approach (PCA) is considered one of the theories identified as the Third Force in Psychology or Humanistic Psychology. There are some significant aspects that estabilsih a relationship between the thought of its founder, Carl Rogers, and some purposes of the humanistic psychology and the existencial philosophy. Even though Rogers's work has not been based on phenomenology, it is possible to realize on his writtings, trhough its several phases, the practice of an attitude like the phenomenological one. Therefore, to consider PCA as a humanistic, existencial and phenomenological take us to some connected issues: 1) What is understood as humanistic? 2) By consequence, what is being human in this theorical point of view? 3) How to think humanism on psychology? 4) What aspects from phenomenology and existencialism can estabilish relationship with theory and method of PCA? This article aims to contribute on the reflexion about possible relationships between these philosophical theories and Person Centered Approach, a very controversial theme at brazilian context even though there is theorical diversity and a lot of pionts of view about this approach currently.(AU)

El Enfoque Centrado en la Persona (ECP) se considera una de las corrientes identificadas con la tercera fuerza en psicologia o Psicologia Humanista. Hay aspectos importantes que se relacionan el pensamiento de su fundador, Carl Rogers, con algunos supuestos de la psicología humanista y de la filosofia existencialista. Aunque su trabajo no haya sido orientado por la fenomenologia, percibe en su obra, dividida en varias fases, la práctica de una actitud esta naturaleza. Considerar, por lo tanto, el ECP, como un enfoque humanístico, existencial y fenomenológico nos lleva a uma serie de preguntas relacionadas: 1) ?qué se entiende por humanista? 2) Por consiguiente, ?qué es ser humano en este enfoque? 3) ?Comó pensar humanismo en la psicología? 4) ?Cualés aspectos derivados de la fenomenología y de lo existencialismo encuentran resonancia con la teoría y el metodo del ECP? Este artículo tiene como objetivo contribuir en la reflexión sobre las posibles correlaciones entre las perspectivas filosoficas y el Enfoque Centrado en la Persona, tema aún polémico en el contexto brasileño mismo ante la diversidad teórica y de perspectivas que este enfoque ha asumido hoy.(AU)

Modelagem conceitual do sistema de banco de dados ProteinWorldDB / Conceptual modeling of the database system ProteinWorldDB

Esta tese descreve o projeto conceitual do sistema de banco de dados ProteinWorldDB (PWDB). Um ponto importante da proposta do PWDB é permitir a construção de consultas e procedimentos no domínio da genômica comparativa sem a necessidade de comparação de sequências. Além disso, o PCG comparou milhões de sequências de proteína, incluindo o conjunto proteico total de centenas de genomas completos, utilizando programação dinâmica, e não um método heurístico, para os cálculos de similaridade. A estratégia do PCG, assim como a genômica, está fundamentada no conhecimento de que sequências biológicas por si só são pouco informativas; elas precisam ser analisadas a partir de um enfoque comparativo para a inferência de homologia. A comparação de sequências de diferentes organismos introduz uma perspectiva evolutiva ao processo, e o estudo comparativo de genomas completos pode ampliar a escala do conhecimento de um único processo biológico para o de sistemas biológicos complexos em células e organismos. Para responder eficientemente questões dessa natureza, o esquema conceitual apresentado associa bases de dados biológicos de referência aos índices de similaridade já pré-calculados e armazenados pelo PCGUtilizando um formato gráfico de fácil compreensão para representar conceitos e relacionamentos (diagrama ER), o esquema foi proposto para facilitar o planejamento de consultas e procedimentos por pesquisadores da área de genômica (sem conhecimento de linguagens de bancos de dados), assim como guiar o desenvolvimento e a implementação física do PWDB por profissionais da área de computação. Alguns exemplos são apresentados com o objetivo de demonstrar a utilização do esquema conceitual para a especificação de consultas e procedimentos, mesmo antes da existência de um esquema lógico...

This thesis describes the conceptual design of the database system ProteinWorldDB(PWDB). An important point of the PWDB proposal is to allow the construction of queriesand procedures in the field of comparative genomics without the need for sequencecomparison. Moreover, the PCG compared millions of protein sequences, including theentire set of proteins from hundreds of complete genomes using dynamic programming,rather than a heuristic method, for calculating similarityPCG‘s strategy, like that of genomic studies in general, is grounded in the knowledgethat biological sequences alone are uninformative. They need to be analyzed from acomparative approach to infer homology. The comparison of sequences from differentorganisms introduces an evolutionary perspective to the process and the comparativestudy of complete genomes can expand our knowledge from a single biological processall the way to complex biological systems in cells and organisms. To efficiently answerquestions of this nature, the conceptual schema links selected international referencebiological databases to similarity indexes already precomputed and stored by the PCG.By using an easily understandable graphic format to represent concepts andrelationships (ER diagram), the schema was proposed to help the design of queries andprocedures by genomic researchers (who may not have knowledge of databaselanguages) as well as to guide the development and physical implementation of thesystem by developers. Some examples are presented to demonstrate the use of theconceptual schema for specifying queries and procedures, even before the existence ofa logical schema. The schema can be easily extended. Additional modules can be inserted/removed toinclude other protein sequences comparisons projects that may benefit from theinformation provided by the schema´s central module. Likewise, new databases specificto different areas (-omics, for example) can be cross-referenced to the schema...

Um estudo crítico das psicoterapias fenomenológico-existenciais: terapia centrada na pessoa e Gestalt-terapia / A critical study of phenomenological-existential psychotherapies: person-centered therapy and Gestalt therapy

Este estudo consiste em uma pesquisa teórica que objetiva desenvolver reflexões críticas sobre as bases epistemológicas da Terapia Centrada na Pessoa e da Gestaltterapia, configuradas nas matrizes conceituais elaboradas por Carl Rogers e por Frederick Perls. Analisa algumas re-configurações teóricas dessas psicoterapias propostas por autores brasileiros a partir da articulação com determinados conceitos da fenomenologia de Martin Heidegger. As teorias psicoterápicas, de um modo geral, ainda mantêm uma concepção de sujeito abstrato e descontextualizado historicamente. O mundo hoje nos coloca diante de grandes desafios, em que são necessárias novas formas de compreensão da existência humana e um fazer clínico que dê suporte aos sofrimentos do homem contemporâneo. O percurso metodológico utilizado no estudo constou de: 1. Seleção de textos clássicos para compor as matrizes epistemológicas das psicoterapias centrada na pessoa e gestáltica; 2. Triagem de material produzido por autores que apresentam análise crítica referente ao tema; 3. Sistematização de categorias conceituais da matriz das respectivas psicoterapias; 4. Análise e discussão de alguns temas presentes em publicações nacionais que indicam pontos de re-configurações das matrizes. Dentre os indicativos apontados pelos autores investigados, foi possível destacar: a necessidade de incluir na teoria centrada na pessoa, o estranho, à falta, como condição de possibilidade da existência; superação do conceito de essência, na teoria gestáltica; ressonâncias da concepção heideggeriana de angústia para a prática clínica, já que esta não é concebida enquanto um sintoma psicopatológico a ser extinto ou um distúrbio funcional; assim como dos conceitos de abertura e cuidado, que possibilita pensar a função terapêutica como a de ajudar o cliente a interpretar-se a si mesmo, devolvendo-o ao seu próprio cuidado de maneira mais livre e responsável. Concluímos que, apesar da necessidade de mais estudos a respeito do tema, já há na atualidade um movimento por parte de alguns psicólogos em lançar um olhar contemporâneo sobre a terapia centrada na pessoa e gestáltica, afastando-se de uma concepção essencialista de sujeito e de uma subjetividade enclausurada.

This study consists on a theoretical research which aims to develop critical reflections on the epistemological bases of the Person Centered Therapy and of the Gestalt-therapy configured in the conceptual matrices elaborated by Carl Rogers and by Frederick Perls. It analyzes some psychotherapies' theoretical new configurations proposed by Brazilian authors, starting from the articulation with Martin Heidegger's certain phenomenology concepts. The psychotherapeutic theories, in general, still maintain a conception of abstract existence out of the historical context. The world today puts us before great challenges, so it is necessary new ways of understanding the human existence and a clinical labor which gives support to the contemporary man's sufferings. The methodological path used in the study consists of: 1. selection of classic texts to compose the epistemological matrices of the person centered therapy and gestalt; 2. selection of material produced by authors that present critical analysis regarding the theme; 3. systemization of conceptual categories of the matrix of the respective psychotherapies; 4. analysis and discussion of some present themes in national publications which indicate points of new configurations of the matrices. Among the indicatives pointed by the investigated authors, it was possible to highlight: the need to include the stranger, the lack, in the person centered therapy as condition of possibility of the existence; overcoming the essence concept in the gestalt therapy; Heidegger's anguish concept resonances for the clinical practice, since that is not understood as a psychopathological symptom to be extinct or a functional disturbance; the opening and care concepts as well which make possible to think the therapeutic function as an aid to the customer to interpret himself, returning to his own care in a free and responsible way. We have come to the conclusion that although more studies regarding the theme are needed, there is already, at the present time, a movement on the part of some psychologists in throwing a contemporary glance on the person centered therapy and gestalt, standing away from an essencialist conception of subject and of a cloistered subjectivity.

ProteinWorldDB: querying radical pairwise alignments among protein sets from complete genomes.

MOTIVATION: Many analyses in modern biological research are based on comparisons between biological sequences, resulting in functional, evolutionary and structural inferences. When large numbers of sequences are compared, heuristics are often used resulting in a certain lack of accuracy. In order to improve and validate results of such comparisons, we have performed radical all-against-all comparisons of 4 million protein sequences belonging to the RefSeq database, using an implementation of the Smith-Waterman algorithm. This extremely intensive computational approach was made possible with the help of World Community Grid, through the Genome Comparison Project. The resulting database, ProteinWorldDB, which contains coordinates of pairwise protein alignments and their respective scores, is now made available. Users can download, compare and analyze the results, filtered by genomes, protein functions or clusters. ProteinWorldDB is integrated with annotations derived from Swiss-Prot, Pfam, KEGG, NCBI Taxonomy database and gene ontology. The database is a unique and valuable asset, representing a major effort to create a reliable and consistent dataset of cross-comparisons of the whole protein content encoded in hundreds of completely sequenced genomes using a rigorous dynamic programming approach. AVAILABILITY: The database can be accessed through http://proteinworlddb.org